title: Phenotypic variance in childhood coeliac disease and the HLA-DQ/DR dose effect.
abstract: OBJECTIVE
  Coeliac disease (CD) is associated with HLA-DQ2 and DQ8. The clinical picture is variable and certain human leucocyte antigen (HLA) DQ/DR combinations have a higher relative risk (RR) for CD than others. Moreover, the HLA-DQ gene-dose effect has an impact on the strength of the gluten-specific T-cell response and thus may correlate with clinical presentation and severity of CD. The aim of this study was to determine the correlation between HLA-DQ/DR-based genotypes and the variation in phenotypes of the disease.
  
  
  METHODS
  A total of 113 non-related Caucasian children clinically diagnosed with CD during the period 1980-2003 with a known HLA type were included in the study. Patients were divided into four categories according to amount of disease expression predisposing to HLA-DQ2 or HLA-DQ8 molecules and the known RR of their HLA-DR/DQ type for CD: high (DR3DQ2 homozygous and DR3DQ2/DR7DQ2), substantial (DR3DQ2/DR5DQ7 and DR5DQ7/DR7DQ2), moderate (DR3DQ2-DR4DQ8 and DR3DQ2/DR*DQ*) and low (DR7DQ2/DR*DQ*, DR4DQ8- DR*DQ* and DR*DQ*- DR*DQ*). The clinical data and HLA genotypes of these patients were compared.
  
  
  RESULTS
  The 113 children were diagnosed with CD at a mean age of 4.6 years and boys were significantly older than girls when diagnosed (p=0.01). RR for having CD was highest for the high HLA-risk group (RR 8.1). With the exception of a greater frequency of abdominal distension and fewer non-gastrointestinal symptoms in the substantial HLA-risk group, there were no significant differences in clinical characteristics or degree of severity of the small-bowel histological findings between the children in the different HLA-risk groups.
  
  
  CONCLUSIONS
  No correlation was found between disease severity and a double HLA-DQ2 gene dose.
authors.affiliation: Department of Paediatric Gastroenterology, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: Beatrijs A N
authors.initials: BA
authors.lastname: Vermeulen
authors.forename: Caroline E
authors.initials: CE
authors.lastname: Hogen Esch
authors.forename: Zehre
authors.initials: Z
authors.lastname: Yuksel
authors.forename: Frits
authors.initials: F
authors.lastname: Koning
authors.forename: Willem
authors.initials: W
authors.lastname: Verduijn
authors.forename: Ilias I N
authors.initials: II
authors.lastname: Doxiadis
authors.forename: Geziena M Th
authors.initials: GM
authors.lastname: Schreuder
authors.forename: M Luisa
authors.initials: ML
authors.lastname: Mearin
mesh_terms: D002446:Celiac Disease / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005983:Glutens / Q000276:immunology; D006683:HLA-DQ Antigens / Q000235:genetics* / Q000276:immunology; D006684:HLA-DR Antigens / Q000235:genetics; D015803:HLA-DR3 Antigen / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008297:Male; D008403:Mass Screening; D010641:Phenotype; D012189:Retrospective Studies; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D006683:HLA-DQ Antigens; C053186:HLA-DQ2 antigen; D006684:HLA-DR Antigens; D015803:HLA-DR3 Antigen; D005983:Glutens